tbuckley/cabot-search huggingface dataset:
Graduate Medical Education
Journal: JAMA (1996)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>Akkermansia muciniphila</i> upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway
Authors: Camille Martin-Gallausiaux, Diego Garcia-Weber, Amandine Lashermes, Pierre Larraufie, Ludovica Marinelli, Veronica Teixeira, Alice Rolland, Fabienne Béguet-Crespel, Vincent Brochard, Timothé Quatremare, Alexandre Jamet, Joël Doré, Scott D. Gray-Owen, Hervé M. Blottière, Cécile Arrieumerlou, Nicolas Lapaque
Journal: Gut Microbes (2022)

The commensal bacteria that make up the gut microbiota impact the health of their host on multiple levels. In particular, the interactions taking place between the microbe-associated molecule patterns (MAMPs) and pattern recognition receptors (PRRs), expressed by intestinal epithelial cells (IECs), are crucial for maintaining intestinal homeostasis. While numerous studies showed that TLRs and NLRs are involved in the control of gut homeostasis by commensal bacteria, the role of additional innate immune receptors remains unclear. Here, we seek for novel MAMP-PRR interactions involved in the beneficial effect of the commensal bacterium Akkermansia muciniphila on intestinal homeostasis. We show that A. muciniphila strongly activates NF-κB in IECs by releasing one or more potent activating metabolites into the microenvironment. By using drugs, chemical and gene-editing tools, we found that the released metabolite(s) enter(s) epithelial cells and activate(s) NF-κB via an ALPK1, TIFA and TRAF6-dependent pathway. Furthermore, we show that the released molecule has the biological characteristics of the ALPK1 ligand ADP-heptose. Finally, we show that A. muciniphila induces the expression of the MUC2, BIRC3 and TNFAIP3 genes involved in the maintenance of the intestinal barrier function and that this process is dependent on TIFA. Altogether, our data strongly suggest that the commensal A. muciniphila promotes intestinal homeostasis by activating the ALPK1/TIFA/TRAF6 axis, an innate immune pathway exclusively described so far in the context of Gram-negative bacterial infections.
Treatment of schizophrenia
Authors: P. Bracken
Journal: BMJ (2000)

# Value of diagnosis of schizophrenia remains in dispute {#article-title-2} EDITOR—Proponents of clinical effectiveness in mental health argue that the problems of psychiatry will be solved by more focused research and a better flow of information from academics to clinicians. A good example of the limitations of this approach is McGrath and Emmerson's review article on the treatment of schizophrenia.1 The authors fail to note that the diagnosis of schizophrenia remains in dispute. The concept has little explanatory power and is scientifically suspect.2 Inclusion in the Cochrane Library does not make it any less controversial. We are not convinced by their calls for prompt diagnosis. In recent years the word schizophrenia has increasingly taken on negative connotations in the public imagination. Telling a young person that he or she has schizophrenia can have devastating results. In ourclinical work with patients we manage perfectly well without using the diagnosis at all. McGrath and Emmerson's review is devoted almost entirely to drug treatments, with only a small section on psychosocial interventions. Users complain that drugs are often all theyreceive when they are in crisis and in need of human interaction and practical support. Perhaps the affiliations noted as the authors' competing interests—substantial linkswith the pharmaceutical industry—go some way towards explaining their narrow vision. We believe that the clinical effectiveness paradigm in mental health will do more harmthan good if it is not balanced by a discourse on what we would call ethical issues. These issues are an examination of the values underlying diagnoses and treatments; a questioning of priorities in our work with people in crisis; an examination of the burden we often inflict with our diagnoses and treatments; and a genuine attempt to listen to what service users are telling us about the nature of care. 1. 1.↵1. McGrath J, 2. Emmerson WB . Treatment of schizophrenia. BMJ 1999; 319: 1045–1048. (16 October.) [OpenUrl][1][FREE Full Text][2] 2. 2.↵1. Boyle M . Schizophrenia: a scientific delusion. London: Routledge, 1993. # What in fact is schizophrenia? {#article-title-4} EDITOR—Without doubt the question "What is schizophrenia?" is a fascinating one. In their … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DMcGrath%26rft.auinit1%253DJ.%26rft.volume%253D319%26rft.issue%253D7216%26rft.spage%253D1045%26rft.epage%253D1048%26rft.atitle%253DFortnightly%2Breview%253A%2BTreatment%2Bof%2Bschizophrenia%26rft_id%253Dinfo%253Apmid%252F10521199%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=319/7216/1045&atom=%2Fbmj%2F320%2F7237%2F800.atom
TIGER: A Web Portal of Tumor Immunotherapy Gene Expression Resource
Authors: Zhihang Chen, Ziwei Luo, Di Zhang, Huiqin Li, Xuefei Liu, Kaiyu Zhu, Hongwan Zhang, Zongping Wang, Penghui Zhou, Jian Ren, An Zhao, Zhixiang Zuo
Journal: Genomics Proteomics & Bioinformatics (2022)

Immunotherapy is a promising cancer treatment method; however, only a few patients benefit from it. The development of new immunotherapy strategies and effective biomarkers of response and resistance is urgently needed. Recently, high-throughput bulk and single-cell gene expression profiling technologies have generated valuable resources. However, these resources are not well organized and systematic analysis is difficult. Here, we present TIGER, a tumor immunotherapy gene expression resource, which contains bulk transcriptome data of 1508 tumor samples with clinical immunotherapy outcomes and 11,057 tumor/normal samples without clinical immunotherapy outcomes, as well as single-cell transcriptome data of 2,116,945 immune cells from 655 samples. TIGER provides many useful modules for analyzing collected and user-provided data. Using the resource in TIGER, we identified a tumor-enriched subset of CD4+ T cells. Patients with melanoma with a higher signature score of this subset have a significantly better response and survival under immunotherapy. We believe that TIGER will be helpful in understanding anti-tumor immunity mechanisms and discovering effective biomarkers. TIGER is freely accessible at http://tiger.canceromics.org/.
Virological features and pathogenicity of SARS-CoV-2 Omicron BA.2
Authors: Jasper Fuk-Woo Chan, Bingjie Hu, Yue Chai, Huiping Shuai, Huan Liu, Jialu Shi, Yuanchen Liu, Chaemin Yoon, Jinjin Zhang, Jing-Chu Hu, Yuxin Hou, Xiner Huang, Terrence Tsz-Tai Yuen, Tianrenzheng Zhu, Wenjun Li, Jian-Piao Cai, Cuiting Luo, Cyril Chik-Yan Yip, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Bao-Zhong Zhang, Jian-Dong Huang, Kelvin Kai-Wang To, Kwok-Yung Yuen, Hin Chu
Journal: Cell Reports Medicine (2022)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 was a dominant circulating SARS-CoV-2 variant worldwide. Recent reports hint that BA.2 is similarly potent regarding antibody evasion but may be more transmissible than BA.1. The pathogenicity of BA.2 remains unclear and is of critical public health significance. Here we investigated the virological features and pathogenicity of BA.2 with in vitro and in vivo models. We show that BA.2 is less dependent on transmembrane protease serine 2 (TMPRSS2) for virus entry in comparison with BA.1 in vitro. In K18-hACE2 mice, BA.2 replicates more efficiently than BA.1 in the nasal turbinates and replicates marginally less efficiently in the lungs, leading to decreased body weight loss and improved survival. Our study indicates that BA.2 is similarly attenuated in lungs compared with BA.1 but is potentially more transmissible because of its better replication at the nasal turbinates.
Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients
Authors: Barbara Mora, Paola Guglielmelli, Andrew Kuykendall, Elisa Rumi, Margherita Maffioli, Francesca Palandri, Valerio De Stefano, Marianna Caramella, Silvia Salmoiraghi, Jean-Jacques Kiladjian, Jason Gotlib, Alessandra Iurlo, Francisco Cervantes, Marco Ruggeri, Richard T. Silver, Francesco Albano, Giulia Benevolo, David M. Ross, Matteo G. Della Porta, Timothy Devos, Giada Rotunno, Rami S. Komrokji, Ilaria C. Casetti, Michele Merli, Marco Brociner, Domenica Caramazza, Giuseppe Auteri, Tiziano Barbui, Daniele Cattaneo, Lorenza Bertù, Luca Arcaini, Alessandro M. Vannucchi, Francesco Passamonti
Journal: Leukemia (2022)
Low-Level Lead Exposure and the IQ of Children
Authors: Herbert L. Needleman
Journal: JAMA (1990)

We identified 24 modern studies of childhood exposures to lead in relation to IQ. From this population, 12 that employed multiple regression analysis with IQ as the dependent variable and lead as the main effect and that controlled for nonlead covariates were selected for a quantitative, integrated review or metaanalysis. The studies were grouped according to type of tissue analyzed for lead. There were 7 blood and 5 tooth lead studies. Within each group, we obtained joint<i>P</i>values by two different methods and average effect sizes as measured by the partial correlation coefficients. We also investigated the sensitivity of the results to any single study. The sample sizes ranged from 75 to 724. The sign of the regression coefficient for lead was negative in 11 of 12 studies. The negative partial r's for lead ranged from —.27 to —.003. The power to find an effect was limited, below 0.6 in 7 of 12 studies. The joint<i>P</i>values for the blood lead studies were &lt;.0001 for both methods of analysis (95% confidence interval for group partial<i>r</i>, —.15±.05), while for the tooth lead studies they were.0005 and.004, respectively (95% confidence interval for group partial<i>r</i>, —.08±.05). The hypothesis that lead impairs children's IQ at low dose is strongly supported by this quantitative review. The effect is robust to the impact of any single study. (<i>JAMA</i>. 1990;263:673-678)
Congestion in heart failure: a circulating biomarker‐based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology
Authors: Julio Núñez, Rafael de la Espriella, Patrick Rossignol, Adriaan A. Voors, Wilfried Mullens, Marco Metra, Ovidiu Chioncel, James L. Januzzi, Christian Mueller, A. Mark Richards, Rudolf A. de Boer, Thomas Thum, Henrike Arfsten, Arantxa González, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Tuvia Ben Gal, Jan Biegus, Alain Cohen‐Solal, Michael Böhm, Michele Emdin, Ewa A. Jankowska, Finn Gustafsson, Loreena Hill, Tiny Jaarsma, Pardeep S. Jhund, Yuri Lopatin, Lars H. Lund, Davor Milicic, Brenda Moura, Massimo F. Piepoli, Piotr Ponikowski, Amina Rakisheva, Arsen Ristic, Gianluigi Savarese, Carlo G. Tocchetti, Sophie Van Linthout, Maurizio Volterrani, Petar Seferovic, Giuseppe Rosano, Andrew J.S. Coats, Antoni Bayes‐Genis
Journal: European Journal of Heart Failure (2022)
Effect of reductions in amyloid levels on cognitive change in randomized trials: instrumental variable meta-analysis
Journal: BMJ (2022)

Bapineuzumab-1, Solanezumab-1, Solanezumab-2, and Gantenerumab.Data for the EMERGE and ENGAGE trials of Aducanumab were previously obtained from the only source available at the time, but cognitive data for these trials were subsequently updated on ClinicalTrials.govand are shown here.Data from a publication available at the time of original publication were replaced with data from ClinicalTrials.gov for Verubecestat-2. 2The updated results do not include data that are not currently publicly available (Lecanemab) or from trials that were not completed at the time of the original publication (Donanemab).Figure 1, figure 2, figure 3, and figure 4 show the updated results.These results do not substantively change the primary results in the original publication: the meta-analyzed estimate of the effect of amyloid reduction on cognitive change as measured with the mini-mental state examination across 40 arms of 14 trials is small and consistent with the null.
S6K1 amplification confers innate resistance to CDK4/6 inhibitors through activating c-Myc pathway in patients with estrogen receptor-positive breast cancer
Authors: Hongnan Mo, Xuefeng Liu, Yu Xue, Hongyan Chen, Shichao Guo, Zhangfu Li, Shuang Wang, Caiming Li, Jiashu Han, Ming Fu, Yongmei Song, Dan Li, Fei Ma
Journal: Molecular Cancer (2022)

CDK4/6 inhibitors combined with endocrine therapy has become the preferred treatment approach for patients with estrogen receptor-positive metastatic breast cancer. However, the predictive biomarkers and mechanisms of innate resistance to CDK4/6 inhibitors remain largely unknown. We sought to elucidate the molecular hallmarks and therapeutically actionable features of patients with resistance to CDK4/6 inhibitors.
Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study
Authors: Evan Y Yu, Josep M Piulats, Gwenaelle Gravis, Peter C C Fong, Tilman Todenhöfer, Brigitte Laguerre, Jose A Arranz, Stephane Oudard, Christophe Massard, Julia Heinzelbecker, Luke T Nordquist, Joan Carles, Michael P Kolinsky, Marinela Augustin, Howard Gurney, Ali Tafreshi, Xin Tong Li, Ping Qiu, Christian H Poehlein, Charles Schloss, Johann S de Bono
Journal: European Urology (2022)

Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC).To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC.Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening.Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily.The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS).Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65-76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22-47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0-6.5) and median OS was 14 mo (95% CI, 10.4-18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3-5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design.Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC.Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.
Mechanisms for Reduced Fibrin Clot Formation on Liquid‐Infused Surfaces
Authors: Jun Ki Hong, Alexander M. Ruhoff, Kavya Mathur, Chiara Neto, Anna Waterhouse
Journal: Advanced Healthcare Materials (2022)

Abstract Biomedical devices are prone to blood clot formation (thrombosis), and liquid‐infused surfaces (LIS) are effective in reducing the thrombotic response. However, the mechanisms that underpin this performance, and in particular the role of the lubricant, are not well understood. In this work, it is investigated whether the mechanism of LIS action is related to i) inhibition of factor XII (FXII) activation and the contact pathway; ii) reduced fibrin density of clots formed on surfaces; iii) increased mobility of proteins or cells on the surface due to the interfacial flow of the lubricant. The chosen LIS is covalently tethered, nanostructured layers of perfluorocarbons, infused with thin films of medical‐grade perfluorodecalin (tethered‐liquid perfluorocarbon), prepared with chemical vapor deposition previously optimized to retain lubricant under flow. Results show that in the absence of external flow, interfacial mobility is inherently higher at the liquid–blood interface, making it a key contributor to the low thrombogenicity of LIS, as FXII activity and fibrin density are equivalent at the interface. The findings of this study advance the understanding of the anti‐thrombotic behavior of LIS‐coated biomedical devices for future coating design. More broadly, enhanced interfacial mobility may be an important, underexplored mechanism for the anti‐fouling behavior of surface coatings.
Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis
Authors: Faizul Hasan, Yu-Kang Tu, Chih-Ming Lin, Li-Pang Chuang, Chii Jeng, Lia Taurussia Yuliana, Ting-Jhen Chen, Hsiao-Yean Chiu
Journal: Sleep Medicine Reviews (2022)
Application of Microbiome in Forensics
Authors: Jun Zhang, Wenli Liu, Halimureti Simayijiang, Ping Hu, Jiangwei Yan
Journal: Genomics Proteomics & Bioinformatics (2022)

Recent advances in next-generation sequencing technologies and improvements in bioinformatics have expanded the scope of microbiome analysis as a forensic tool. Microbiome research is concerned with the study of the compositional profile and diversity of microbial flora as well as the interactions between microbes, hosts, and the environment. It has opened up many new possibilities for forensic analysis. In this review, we discuss various applications of microbiome in forensics, including identification of individuals, geolocation inference, and post-mortem interval (PMI) estimation.
Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression
Authors: Tihong Shao, Patrick S. C. Leung, Weici Zhang, Koichi Tsuneyama, William M. Ridgway, Howard A. Young, Zongwen Shuai, Aftab A. Ansari, M. Eric Gershwin
Journal: Cellular and Molecular Immunology (2022)

Abstract The interferon (IFN) signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of autoimmunity. We have generated a unique murine model named ARE-Del, with chronic overexpression of IFNγ, by altering IFNγ metabolism. Importantly, these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis, including high titers of autoantibodies and portal inflammation. We hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of cholangitis. To study this hypothesis, ARE-Del +/− mice were treated with the JAK1/2 inhibitor ruxolitinib and serially studied. JAK inhibition resulted in a significant reduction in portal inflammation and bile duct damage, associated with a significant reduction in splenic and hepatic CD4 + T cells and CD8 + T cells. Functionally, ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγ and TNF from splenic CD4 + T cells. Additionally, ruxolitinib treatment also decreased the frequencies of germinal center B (GC B) cells and T follicular helper (Tfh) cells and led to lower serological AMA levels. Of note, liver and peritoneal macrophages were sharply decreased and polarized from M1 to M2 with a higher level of IRF4 expression after ruxolitinib treatment. Mechanistically, ruxolitinib inhibited the secretion of IL-6, TNF and MCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro, indicating that M1 macrophage polarization to M2 occurred through activation of the STAT6-IRF4 pathway. Our data highlight the significance, both immunologically and clinically, of the JAK/STAT signaling pathway in autoimmune cholangitis.
Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis
Authors: Kaitlin G. Whaley, Ye Xiong, Rebekah Karns, Jeffrey S. Hyams, Subra Kugathasan, Brendan M. Boyle, Thomas D. Walters, Judith Kelsen, Neal LeLeiko, Jason Shapiro, Amanda Waddell, Sejal Fox, Ramona Bezold, Stephanie Bruns, Robin Widing, Yael Haberman, Margaret H. Collins, Tomoyuki Mizuno, Phillip Minar, Geert R. D’Haens, Lee A. Denson, Alexander A. Vinks, Michael J. Rosen
Journal: Clinical Gastroenterology and Hepatology (2022)
Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1–Notch1
Authors: Rong Chen, Shiqing Zhang, Fang Liu, Lin Xia, Chong Wang, Siamak Sandoghchian Shotorbani, Huaxi Xu, Subrata Chakrabarti, Tianqing Peng, Zhaoliang Su
Journal: Acta Pharmaceutica Sinica B (2022)

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.